Ultrasonic catheter drug delivery method and device

ABSTRACT

An ultrasonic catheter drug delivery device comprises an ultrasound transducer to produce ultrasonic waves, which transducer is mechanically attached to a catheter body or chamber. The ultrasonic transducer has a distal tip with a distal radiation surface, and when a therapeutic agent from a fluid source is directed to the catheter body or chamber, the radiation surface creates ultrasonic pressure and delivers liquid and simultaneously ultrasonic energy to a patient&#39;s vascularity or a selected body lumen. The method applies therapeutic agent and ultrasonic waves to the vascular area, lung or any body lumen without requiring direct contact between ultrasound transducer and body, dissolves blood clots, and stimulates tissue cells.

FIELD OF THE INVENTION

The present invention generally relates to medical devices and methods.More particularly, the present invention relates to apparatus andmethods for the ultrasonically enhanced delivery of therapeutic orcontrast agents within the vascular and lung areas or other corporeallumens.

BACKGROUND OF THE INVENTION

Despite the significant progress of medical technology, vascular andlung diseases, as well as arterial thrombosis (blood clots in arteries),remain frequent, costly and serious problems in health care. Currentmethods of treatment such as drugs, interventional devices, and/orbypass surgery are usually expensive and not always effective, evensometimes causing additional problems. For example, drugs can alsodissolve beneficial clots or interventional devices can injure healthytissue to cause potentially fatal bleeding complications or to formscarring or cellular growth which may itself eventually become a seriousobstruction in, for example, a blood vessel (a process known asrestenosis).

Ultrasonic energy has been used for enhancing the intravascular deliveryof drug, to dissolve clot acoustically, disrupt mechanically and inhibitrestenosis. Such energy can be delivered intravascularly usingspecialized catheters having ultrasonically vibrating surface at or neartheir distal ends. One type of ultrasonic catheter delivery system usesa wire or other axial transmission element to deliver energy from anultrasonic energy source, located outside the patient to the internalorgans, to desired corporeal lumens. (See, for example, U.S. Pat. Nos.5,002,059, 5,324,255, 5,345,940, and 5,699,805, each of which isincorporated herein by reference.) Such catheters are rigid and cannotbe easily inserted through narrow and tortuous vessels and may causeserious damage to vascular walls.

A second type of catheter has ultrasonic transducers mounted directly ontheir distal ends. See, for example; U.S. Pat. Nos. 5,362,309,5,318,014, 5,315,998, 5,269,291, 5,197,946, 6,001,069, and 6,024,718,each of which is incorporated herein by reference. Despite enhancedsafety and the fact that there is no need to employ a transmissionelement along the entire length, these catheters suffer from limitedultrasound energy, and the transducer-catheter design is stillproblematic.

Another type of catheter has an ultrasonic transducer or ultrasoundtransmission element with a central orifice in the distal end to impartultrasonic energy into liquid and simultaneously deliver it to acorporeal lumen. See, for example, U.S. Pat. Nos. 5,735,811 and5,197,946, each of which is incorporated herein by reference. Althoughthese catheters are more effective and liquid delivery is moreconvenient, there are design difficulties and limitation of ultrasoundenergy from longitudinal waves.

OBJECT OF THE INVENTION

It is an object of the invention to provide an improved method anddevice for catheter drug delivery.

It is also an object of this invention to provide a method and devicefor catheter drug delivery using ultrasound energy.

It is another object of the invention to mix different drugsultrasonically and deliver them to a desired corporeal lumenultrasonically.

It is a yet another object of the invention to mix drug-liquid solutionswith a gas (for example, saline with oxygen) ultrasonically and deliverthe mixture to a desired corporeal lumen ultrasonically.

It is a further object of the invention to provide a method and devicefor delivering drugs to an intravascular area or/and a corporeal lumen,to dissolve blood clots.

It is a yet further object of the invention to treat a blocked andnarrowed blood vessel with ultrasound waves.

These and other objects of the invention will become more apparent fromthe discussion below.

SUMMARY OF THE INVENTION

The present invention relates to apparatus and method for theultrasonically enhanced delivery of therapeutic or contrast agentswithin the vascular and lung area or other desired corporeal lumens.Ultrasonic waves are applied to a vascular area, lung or any corporeallumen without requiring direct contact between ultrasound transducer tipand the patient's body, particularly to dissolve blood clots.

According to the present invention, a catheter system comprises anultrasound transducer having a distal tip with a radial surface and adistal end surface. The ultrasound transducer is disposed in a chamberat the proximal end of the catheter, and the transducer radiationsurface or tip directs ultrasound waves or energy forward into thecatheter coaxially via liquid. Longitudinal ultrasound waves induce wavemotion in fluid adjacent to the transducer distal end. Whileparticularly intended to enhance the absorption of therapeutic agentsdelivered to certain body lumens, the catheter system of the presentinvention is also useful for the delivery of ultrasonic energy to adesired location. The transducer radiation surface or transducer tip,may be cylindrical, flat, concave, convex, irregular or have a differentshape-geometry to radiate ultrasound energy into catheter.

The catheter of the present invention may comprise a proximal tubing fordelivering therapeutic agent from a reservoir by pump or syringe. Thetubing may be located in front of or behind the radiation surface.

In a first embodiment of the invention, an ultrasound transducer and tipare mounted in a proximal portion of a catheter body, located outside ofthe body of a patient. The remainder of the catheter distal to theproximal portion may be inserted into a blood vessel or attached to abody lumen, to drive a therapeutic agent ultrasonically and/or deliverultrasonic energy.

In a second embodiment, the distal tip of the transducer does not havean orifice, which is very important to create and deliver ultrasoundenergy fully to a vessel or body lumen.

In a third embodiment, the catheter system comprises a catheter body,mechanically coupled with an ultrasound transducer through a housing ortip node, which is where the transducer body is outside the catheter. Inthis way, the catheter body can be provided with two or more tubinginlets (sleeves) for different therapeutic agents, even one or moredifferent gases such as oxygen, and agents to be mixed and deliveredultrasonically.

The catheter system of the invention is particularly advantageous ontissues for which local topical application of a therapeutic agent isdesirable but contact with the tissue is to be avoided. Furthermore,ultrasound waves used in the method energize the drug, dissolve theclots and cause the penetration of the drug within the narrow andblocked vessels.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective, partly cross-sectional view of an ultrasoniccatheter drug delivery system for use according to the presentinvention;

FIG. 2 is a lateral view of an ultrasonic catheter system chamber of theinvention with two horizontally located sleeves;

FIG. 3 is a frontal view of an ultrasonic catheter system chamber of theinvention with three peripherally located sleeves;

FIG. 4 is a lateral, cross-sectional view of a catheter system chamber,mechanically coupled with an ultrasound transducer through the tip; and

FIG. 5 is a lateral, cross-sectional view of an ultrasonic catheter drugdelivery system for delivering therapeutic agent to the catheter body orchamber through a central orifice of the ultrasonic tip.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is a method and device, which provides treatmentof luminal conditions, particularly for the treatment of coronary andperipheral arterial disease and thrombosis, where the purpose is todissolve or disrupt the clot, plague or other stenotic lesions whichcause the disease, and for dilation of narrowed vessels. The method anddevice of the present invention also useful to enhance theadministration of therapeutic agents primarily responsible for thedisruption of the clots or other stenotic material. The ultrasonicenergy agitates and promotes the penetration of the drug into thestenotic material. Due to delivery of therapeutic agent and ultrasoundenergy through the agent, this method and device of the presentinvention are further useful for treatment of other body lumens, such asthe urethra, ureter, fallopian tubes, or urological disorders relatedwith prostate gland (BPH—Benigh Proctatic Hyperplasia), and can be usedfor impotency (erectile dysfunction) treatment by ultrasonicallystimulating sexual organs, urinary tract, and the like.

The present invention can be used for targeted and localized drugdelivery for treatment of lung, vasculature, vasopasm and tumortreatment. In addition, this invention is very useful for the treatmentof closed wounds as a fistulas, canals, etc., by destroying bacteriacells and stimulating healthy tissue cells.

The invention can perhaps be better appreciated by referring to thedrawings. FIG. 1 is a perspective view of ultrasound catheter drugdelivery system 2, comprising an ultrasound generator 4, a connector 6operatively connecting ultrasound generator 4 with a transducer 8, ahousing 10 surrounding transducer 8, and a catheter 12 having a proximalportion 14 with a chamber 16 containing a therapeutic agent 18.Transducer 8 has a tip 20 with a radial surface 22 and a distalradiation surface 24. Chamber 16 is in fluid communication throughtubing 26 with a fluid source 28, and directly with at least one lumen30 of the distal portion 32 of catheter 12 that extends to catheterdistal end 34. Fluid source 28 can be, for example, a reservoir with apressure pump or syringe.

The proximal section 36 of catheter proximal portion 14 sealinglyengages housing 10. Preferably the inner surface 38 of proximal section36 has threads 40 that engage reciprocal threads 42 on the outer surface44 of housing 10. This arrangement will allow the operator to vary thedistance between distal radiation surface 24 and the distal end 46 ofchamber 16 to regulate ultrasonic pressure and energy level. Whileradial surface 22 can be smooth or substantially smooth, it is preferredthat this surface is not smooth, for example, with rings, threads,barbs, or the like, which will create more ultrasonic pressure incatheter 12.

In the embodiment of the invention shown in FIG. 1, ultrasonic energy ata pre-selected frequency is sent through the catheter 10 with fluid suchas a therapeutic agent as a transmission member. Ultrasound energy willpass through therapeutic agent 18 to catheter distal end 34. Catheter 12may be formed from a conventional rigid or flexible material, dependentupon the application. It would be appropriate for catheter 12 to beflexible if the catheter is to be inserted into tortuous vascularity orif catheter distal end 34 is to be attached to a vessel, fistula, or thelike.

It is provided that the distal radiation surface is driven with aconstant, modulated or pulsed frequency. It is also provided that thedistal radiation surface is driven with a sinusoidal, rectangular,trapezoidal or triangular wave form. It is further provided that thetransducer is capable of being operated at a frequency from 10 kHz to10,000 MHz.

A second embodiment of the invention is shown in FIG. 2, wheretransducer 50 is fixedly, optionally removably, attached to the proximalsection 52 of the proximal portion 54 of a catheter 56. Transducer 50has a tip 58 with a radial surface 60 and a distal radiation surface 62.Catheter proximal portion 54 has a chamber 64 with a therapeutic agent66 that is in fluid communication with each of two fluid sources 68,70through lumens 72,74, respectively. Fluid sources 68,70 may provide twoor more fluids, e.g., liquid or gas, such as saline or oxygen, to beultrasonically mixed and delivered through lumen 76 to catheter distalend 78.

FIG. 3 is a semi-cross-sectional view of the proximal end of a catheteraccording to the invention wherein three fluid sources 80 are each influid communication through a lumen 82 with chamber 84 of catheterproximal section 86. The distal radiation surface 88 of a transducer(not shown) is positioned within chamber 84.

In FIG. 4, a connector 110 operatively connects an ultrasound generator(not shown) with a transducer 112, which has a tip 114 with a radialsurface 116 and a distal end surface 118. A catheter 120 has a proximalportion 122 with a chamber 124 containing a therapeutic agent 126.Chamber 124 is in fluid communication through tubing 130 with a fluidsource 132, and directly with at least one lumen 134 of the distalportion 136 of catheter 120 that extends to catheter distal end 140.Fluid source 132 can be, for example, a reservoir with a pressure pumpor syringe.

The proximal section 142 of catheter proximal portion 122 sealinglyengages radial surface 116. Chamber 124 must be attached to ultrasonictransducer distal tip 114 at the mechanical resonant node, such as node144. If chamber 124 is not connected to the resonant node (either alittle before or a little after the mechanical node), the intensity ofthe ultrasound energy at distal end 140 will be attenuated, i.e.,damped, and ultrasound waves and/or energy will be transferred to thewalls of chamber 126, possibly damaging the chamber 126 structureassembly, which may cause leakage.

In the embodiment of the invention set forth in FIG. 5, a connector 150operatively connects an ultrasound generator (not shown) with atransducer 152, which has a distal tip 154 with a radial surface 156 anda distal end surface 158. A catheter 160 has a proximal portion 162 witha chamber 164 containing a therapeutic agent 166.

Transducer distal tip 154 has a central orifice 170. Chamber 164 is influid communication with at least one fluid source 172 through centralorifice 170, which can be smooth, waved, ringed, slotted, grooved, orthreaded, and infusion lumen 174 within tubing 176. Two or more fluidsources 172 and infusion lumens 174 can mix and deliver differenttherapeutic agents. Chamber 164 is also in fluid communication withlumen 180 in the distal portion 182 of catheter 160 that extends todistal end 184. The non-smooth surface of orifice 170, such as rings orthreads, increases the pressure of liquid in chamber 164.

Chamber 164 should be attached to ultrasonic transducer distal tip 158at a mechanical resonant node, such as node 190. Similarly, each lumen174 should intersect central orifice 170 at a resonant node, such asnode 192.

The catheter systems herein are comprised of conventional materials. Thetransducer and catheter chamber are preferably comprised of suitablemetallic or even polymeric substances. Most preferably the transducerdistal tip is comprised of a metal such as titanium or nitinol.

As is mentioned throughout, the invention here can deliver one or moreliquid or gaseous substances to a catheter distal end. Such substancesinclude, but are not limited to, therapeutic agents such as antibioticsor antiseptics, saline, oil, water, oxygen, anticoagulants such asheparin or cumadine, or even liquid medical polymers, or mixtures of twoor more thereof.

The preceding specific embodiments are illustrative of the practice ofthe invention. It is to be understood, however, that other expedientsknown to those skilled in the art or disclosed herein, may be employedwithout departing from the spirit of the invention or the scope of theappended claims.

What is claimed is:
 1. A catheter system for ultrasoand drug delivery,comprising: a catheter having a proximal portion comprising a chamberand a distal end, wherein at least one lumen extends longitudinally fromsaid chamber to said distal end; at least one fluid source in fluidcommunication with said chamber; and an ultrasound transducer having adistal end, said distal end extending coaxially into said catheterchamber, wherein said transducer generates ultrasound waves propagatedby the at least one fluid within at least a portion of said catheterinducing wave motion in said fluid to deliver fluid and/or ultrasoundenergy to the catheter distal end.
 2. The catheter system of claim 1,wherein the transducer distal tip is positioned coaxially within thechamber.
 3. The catheter system of claim 1, wherein wave motion isinduced in fluid adjacent to the transducer distal end.
 4. The cathetersystem of claim 1, wherein liquid and ultrasound energy are deliverysimultaneously to the catheter distal end.
 5. The catheter system ofclaim 1, wherein the transducer distal tip has a central orifice influid communication with at least one fluid source and said chamber. 6.The catheter system of claim 5, wherein the surface of the orifice isnon-smooth.
 7. The catheter system of claim 6, wherein the orificesurface is ringed, slotted, waved, grooved, or threaded.
 8. The cathetersystem of claim 5, wherein there are at least two fluid sources andfluids from the fluid sources are admixed in the orifice.
 9. Thecatheter system of claim 1, wherein the transducer is capable ofoperating at a frequency of from about 10 kHz to 10³ MHz.
 10. Thecatheter system of claim 1, wherein the transducer distal tip comprisesa radial surface and a distal radiation surface.
 11. The catheter systemof claim 10, wherein the radial surface is not smooth.
 12. The cathetersystem of claim 11, wherein the radial surface is ringed, slotted,waved, grooved, or threaded.
 13. The catheter system of claim 10,wherein the distal radiation surface is flat, conical, oval, circular,semi-spherical, square, or rectangular.
 14. The catheter system of claim1, wherein the fluid is a therapeutic agent.
 15. The catheter system ofclaim 1, wherein the ultrasound transducer is connected to the proximalportion of the catheter.
 16. The catheter system of claim 1, wherein theultrasound transducer or distal tip can be moved backward or forwardtoward the catheter body to change ultrasound pressure and/or deliveredultrasound energy level.
 17. A method for ultrasonically treating aninterior area of the body, the method comprising the steps of: providinga catheter having at least one lumen; providing a transducer having adistal radiation surface configured and dimensioned in said catheter forcoupling with a proximal end of the catheter and for emitting ultrasonicenergy therein; introducing at least one fluid within the proximal endof the catheter; and delivering the emitted ultrasonic energy to theinterior area of the body by the at least one fluid through the at leastone lumen for treating the interior area of the body with ultrasonicenergy.
 18. The method according to claim 17, wherein the transduceroperates at a frequency from 10 kHz to 10,000 MHz.
 19. The methodaccording to claim 17, wherein the at least one fluid includes one ormore components selected from the group consisting of antibiotics,antiseptics, saline, oils, anticoagulants, and water.
 20. The methodaccording to claim 17, wherein the step of delivering the emittedultrasonic energy to the interior area of the body causes a therapeuticeffect to occur within the body, and wherein the therapeutic effect isselected from the group consisting of increasing blood flow bydecreasing the amount of stenosis within a body lumen, stimulating cellgrowth, alleviating urological disorders, and treating impotency. 21.The method according to claim 17, wherein the transducer is driven by atleast one of a constant, pulsed, and modulated frequency, and whereinthe driving wave form of the transducer is selected from the groupconsisting of sinusoidal, rectangular, trapezoidal and traingular waveforms.
 22. The method according to claim 17, further comprising the stepof translating the distal radiation surface within the proximal end ofthe catheter for regulating at least one characteristic of the emittedultrasonic energy.
 23. The method according to claim 17, furthercomprising the step of introducing another fluid within the proximal endof the catheter for intermixing with the at least one fluid and beingdelivered to the interior area of the body.
 24. The method according toclaim 17, wherein the at least one fluid is introduced within theproximal end of the catheter from a corresponding fluid source, andwherein the corresponding fluid source is a reservoir or a syringe. 25.The method according to claim 17, further comprising the step ofsealingly engaging the distal radiation surface within the proximal endof the catheter.
 26. A catheter system for ultrasonically treating aninterior area of the body, the system comprising: a catheter having atleast one lumen; a transducer having a distal radiation surfaceconfigured and dimensioned in said catheter for coupling with a proximalend of the catheter and for emitting ultrasonic energy therein; andmeans for introducing at least one fluid within the proximal end of thecatheter, wherein the emitted ultrasonic energy is delivered to theinterior area of the body by the at least one fluid through the at leastone lumen for treating the interior area of the body with ultrasonicenergy.
 27. The catheter system according to claim 26, wherein thetransducer operates at a frequency from 10 kHz to 10,000 MHz.
 28. Thecatheter system according to claim 26, further comprising means fortranslating the distal radiation surface within the proximal end of thecatheter for regulating at least one characteristic of the emittedultrasonic energy.
 29. The catheter system according to claim 26,further comprising means for introducing another fluid within theproximal end of the catheter for intermixing with the at least one fluidand being delivered to the interior area of the body.
 30. The cathetersystem according to claim 26, further comprising means for sealinglyengaging the distal radiation surface within the proximal end of thecatheter.
 31. An internal localized bacterial infection treatment methodcomprising the steps of: inserting an ultrasound emitting catheter intoa body to be treated, wherein said ultrasound catheter comprises of anultrasound transducer with a distal radiation end positioned within acatheter chamber and in fluid communication with the catheter distal tipthrough said chamber and a lumen, wherein said fluid transmitsultrasonic energy from the transducer to catheter distal tip; guidingthe catheter to the site of a localized bacterial infection; andemitting ultrasonic energy to impact the site of the localizedinfection.
 32. A treatment method as in claim 31, wherein the ultrasoniccatheter has a user-adjustable ultrasonic frequency range including atleast a plurality of frequencies between 10 kHz and 1000 MHz.
 33. Aninternal treatment method comprising the steps of: inserting anultrasound emitting catheter into a body to be treated, said ultrasoundcatheter comprises of an ultrasound transducer with a distal radiationend positioned within a catheter chamber and in fluid communication withthe catheter distal tip through said chamber and a lumen, wherein saidfluid transmits ultrasonic energy from the transducer to catheter distaltip; guiding the catheter to treatment site; and emitting ultrasonicenergy to impact the treatment site.
 34. A treatment method as in claim33, wherein the ultrasonic catheter has a user-adjustable ultrasonicfrequency range including at least a plurality of frequencies between 10kHz and 1000 MHz.
 35. A treatment method as in claim 33, wherein saidtreatment is beneficial for the promotion of healthy tissue growth ortreatment of conditions in the group consisting of ailments affectingurethra, ureter, and fallopian tubes, impotency, and urologicaldisorders related with prostate gland.
 36. A method for ultrasonicallymixing multiple therapeutic fluids and delivering said mixed fluids tointernal treatment site comprising the use of an ultrasound emittingcatheter, wherein said catheter is comprised of: a chamber in fluidcommunication with a plurality of fluid sources; an ultrasoundtransducer with a distal radiation surface in fluid communication withsaid chamber; and a lumen extending longitudinally from said chamber tothe catheter distal tip and in fluid communication therein.
 37. A methodas in claim 36, wherein said ultrasound transducer has a user-adjustableultrasonic frequency range including at least a plurality of frequenciesbetween 10 kHz and 1000 MHz.